The expression and function of RASAL2 in renal cell carcinoma angiogenesis

Ke Hui, Yangyang Yue, Shiqi Wu, Yanan Gu, Bing Guan, Xinyang Wang, Jer Tsong Hsieh, Luke S. Chang, Dalin He, Kaijie Wu

Research output: Contribution to journalArticle

Abstract

Patients with renal cell carcinoma (RCC) often develop resistance to antivascular drugs and eventually succumb to disease. However, the underlying molecular mechanism remains poorly understood. In this study, we demonstrated that RASAL2, a RAS GTPase-activating protein, played a tumor-suppressive role in RCC by targeting tumor angiogenesis. Firstly, we showed that RASAL2 was frequently epigenetically silenced in RCC, and its loss was negatively correlated with overall survival of RCC patients. Furthermore, we discovered that RASAL2 could inhibit RCC angiogenesis in vitro and in vivo. Mechanistically, we identified that RASAL2 could activate GSK3β by reducing Ser9 phosphorylation and subsequently decrease the expression of c-FOS and vascular endothelial growth factor A (VEGFA). Interruption of the p-GSK3β/c-FOS pathway with the specific inhibitor or small interfering RNA could reverse the expression of VEGFA, which may provide a new insight to prevent RCC from resistance to antivascular therapy.

Original languageEnglish (US)
Article number881
JournalCell Death and Disease
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2018

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Renal Cell Carcinoma
Vascular Endothelial Growth Factor A
GTPase-Activating Proteins
Small Interfering RNA
Neoplasms
Phosphorylation
Survival
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

The expression and function of RASAL2 in renal cell carcinoma angiogenesis. / Hui, Ke; Yue, Yangyang; Wu, Shiqi; Gu, Yanan; Guan, Bing; Wang, Xinyang; Hsieh, Jer Tsong; Chang, Luke S.; He, Dalin; Wu, Kaijie.

In: Cell Death and Disease, Vol. 9, No. 9, 881, 01.09.2018.

Research output: Contribution to journalArticle

Hui, K, Yue, Y, Wu, S, Gu, Y, Guan, B, Wang, X, Hsieh, JT, Chang, LS, He, D & Wu, K 2018, 'The expression and function of RASAL2 in renal cell carcinoma angiogenesis', Cell Death and Disease, vol. 9, no. 9, 881. https://doi.org/10.1038/s41419-018-0898-x
Hui, Ke ; Yue, Yangyang ; Wu, Shiqi ; Gu, Yanan ; Guan, Bing ; Wang, Xinyang ; Hsieh, Jer Tsong ; Chang, Luke S. ; He, Dalin ; Wu, Kaijie. / The expression and function of RASAL2 in renal cell carcinoma angiogenesis. In: Cell Death and Disease. 2018 ; Vol. 9, No. 9.
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AU - Wang, Xinyang

AU - Hsieh, Jer Tsong

AU - Chang, Luke S.

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